It is well established both in experimental animals and humans that adult, fully differentiated hepatocytes have the capacity to undergo replication in response to reduced liver mass. However, it has recently been demonstrated that rat liver contains a stem cell compartment that under certain conditions, become the main source of new hepatocytes in response to reduced liver mass. Exposure to low levels of hepatotoxins (including hepatocarcinogens) that inhibit and/or delay the normal compensatory growth response of normal adult hepatocytes is one condition in which this stem cell compartment is activated. Since high incidence areas for HCC frequently have in common high incidence of HBV infections and exposure to hepatotoxins/hepatocarcinogens, such as aflatoxins and nitrosamines, it seems possible that pathogenesis of HCC mat, at least in part, involve activation of the stem cell compartment in human liver. Little information is available regarding the role of the stem cell compartment in human liver in HCC ther chronic liver diseases. We have therefore decided to investigate the possible existence and role of the stem cell compartment in the pathogenesis of HCC by establishing a contract with the Cancer Institute, Chinese Academy of Medical Science, Beijing, and the Qidong Liver Cancer Institute, Jiangsu, China. It is important to emphasize the prospective nature of the study and consequently the possibility of monitoring the progress of the neoplastic process in terms of both cellular and molecular events.